Clinical immunotherapy trials of bacterial components derived from Mycobacteria and Nocardia.

Preparations of oil-attached mycobacterial components have been used in place of viable bacille Calmette-Guérin (BCG) in animal models and humans as a cancer immunotherapeutic agent. Most preparations consist of the isolated mycobacterial cell wall or cell wall skeleton attached to oil. Cord factor (trehalose dimycolate) has also been included in some preparations. In animal models, such preparations given intralesionally, systemically, or as a vaccine can cause regression of disease and establish tumor-specific immunity. Trials in humans have utilized oil-attached mycobacterial components given intralesionally, intradermally, intrapleurally, intraperitoneally, intravenously, and as an ointment. The major toxicity has been fever, chills, and local inflammation and/or abscess formation. An increase in the white blood count and lymphocyte count has been observed. An increase in liver function test was reported in a minority of patients. Given intralesionally, these preparations cause regression of the injected lesion, regression of noninjected cutaneous and visceral disease, and the apparent establishment of a tumor-specific immune response. Administered intrapleurally and intraperitoneally, there is a response and a clearing of malignant cells in approximately 50% of cases. Given intravenously, oil-attached cell wall skeleton and trehalose dimycolate can eradicate pulmonary disease. Used as an ointment, the preparations have been effective in mycosis fungoides and Kaposi's sarcoma. These reagents demonstrate definite single-agent activity. This was most prominent in patients who were immunocompetent and who had immunogenic tumors such as malignant melanomas. The reagents represent potent immunotherapeutic agents with acceptable toxicity. Further trials of these and subsequent refined preparations are warranted.